Cancer Immunotherapy Harnessing Innate and Adaptive Immune Effector Cells and PD-1 Immune Checkpoint Inhibitors

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 1344

Special Issue Editor

Center for Medical Innovation, Nagasaki University, Nagasaki 852-8588, Japan
Interests: γδ T cell; NK cell; cancer immunotherapy; PD-1; IL-18; adoptive transfer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The idea of harnessing a patient’s immune system to combat cancer originated in the nineteenth century. Wilhelm Busch and Friedrich Fehleisen first described the association between the spontaneous regression of tumors and the development of erysipelas, induced by Streptococcus pyogenes. Subsequently, William B. Coley treated sarcoma patients with cultured streptococci, observing the shrinkage in malignant tumors. This suggested, of course, that the immune system, stimulated by infections, might be responsible for tumor regression. Based on these initial observations on the possible link between infections and tumor rejection, many researchers began to explore the development of immunotherapy of cancer. Most of the attempts were, however, unsuccessful until recently, owing to the lack of reproducibility, coupled with the complexity of the immune system.

The development of immune checkpoint inhibitors—anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) mAb, anti-programmed death-1 (PD-1) mAb and anti-PD-1 ligand 1 (PD-L1) mAb, and chimeric antigen-receptor (CAR)-T cells—suddenly revolutionized cancer treatments in 2010s. The immune checkpoint molecules are physiologically negative regulators of T-cell activation and maintain self-tolerance. The rationale of immune checkpoint therapy is to target the host immune system, in particular, T cells. However, this does not impact malignant tumors per se, as in conventional treatments like chemotherapy and radiotherapy.  CAR-T cells-based therapy is successful for the treatment of B lymphoma. While the introduction of the immune checkpoint inhibitors and CAR-T cells has opened a new era for cancer therapy, the efficacy of the techniques is not yet satisfactory. It is thus imperative to further develop novel cancer immunotherapies, including both PD-1 immune checkpoint combination therapy and the adaptive transfer of immune effector cells, such as genetically- or chemically-modified CAR-T cells, γδ T cells, and NK cells. In order to improve the efficacy of such novel cancer treatments, it is essential to delineate the precise mechanism underlying the effect of modified immune effector cells on tumor cells. Within this Special Issue of Cells, we will highlight the molecular mechanisms and future directions of PD-1 immune checkpoint inhibitor combination therapy and immune effector cells-based immunotherapies. To this end, we invite the submission of original articles and reviews in this exciting field of research.

Prof. Dr. Yoshimasa Tanaka
Guest Editor

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Keywords

  • PD-1 immune checkpoint
  • CAR-T cells
  • γδ T cells
  • NK cells

Published Papers (1 paper)

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Research

19 pages, 5971 KiB  
Article
Development of Innate-Immune-Cell-Based Immunotherapy for Adult T-Cell Leukemia–Lymphoma
Cells 2024, 13(2), 128; https://doi.org/10.3390/cells13020128 - 10 Jan 2024
Viewed by 1022
Abstract
γδ T cells and natural killer (NK) cells have attracted much attention as promising effector cell subsets for adoptive transfer for use in the treatment of malignant and infectious diseases, because they exhibit potent cytotoxic activity against a variety of malignant tumors, as [...] Read more.
γδ T cells and natural killer (NK) cells have attracted much attention as promising effector cell subsets for adoptive transfer for use in the treatment of malignant and infectious diseases, because they exhibit potent cytotoxic activity against a variety of malignant tumors, as well as virus-infected cells, in a major histocompatibility complex (MHC)-unrestricted manner. In addition, γδ T cells and NK cells express a high level of CD16, a receptor required for antibody-dependent cellular cytotoxicity. Adult T-cell leukemia–lymphoma (ATL) is caused by human T-lymphotropic virus type I (HTLV-1) and is characterized by the proliferation of malignant peripheral CD4+ T cells. Although several treatments, such as chemotherapy, monoclonal antibodies, and allogeneic hematopoietic stem cell transplantation, are currently available, their efficacy is limited. In order to develop alternative therapeutic modalities, we considered the possibility of infusion therapy harnessing γδ T cells and NK cells expanded using a novel nitrogen-containing bisphosphonate prodrug (PTA) and interleukin (IL)-2/IL-18, and we examined the efficacy of the cell-based therapy for ATL in vitro. Peripheral blood samples were collected from 55 patients with ATL and peripheral blood mononuclear cells (PBMCs) were stimulated with PTA and IL-2/IL-18 for 11 days to expand γδ T cells and NK cells. To expand NK cells alone, CD3+ T-cell-depleted PBMCs were cultured with IL-2/IL-18 for 10 days. Subsequently, the expanded cells were examined for cytotoxicity against ATL cell lines in vitro. The proportion of γδ T cells in PBMCs was markedly low in elderly ATL patients. The median expansion rate of the γδ T cells was 1998-fold, and it was 12-fold for the NK cells, indicating that γδ T cells derived from ATL patients were efficiently expanded ex vivo, irrespective of aging and HTLV-1 infection status. Anti-CCR4 antibodies enhanced the cytotoxic activity of the γδ T cells and NK cells against HTLV-1-infected CCR4-expressing CD4+ T cells in an antibody concentration-dependent manner. Taken together, the adoptive transfer of γδ T cells and NK cells expanded with PTA/IL-2/IL-18 is a promising alternative therapy for ATL. Full article
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